Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21840 | 65743;65744;65745 | chr2:178583664;178583663;178583662 | chr2:179448391;179448390;179448389 |
| N2AB | 20199 | 60820;60821;60822 | chr2:178583664;178583663;178583662 | chr2:179448391;179448390;179448389 |
| N2A | 19272 | 58039;58040;58041 | chr2:178583664;178583663;178583662 | chr2:179448391;179448390;179448389 |
| N2B | 12775 | 38548;38549;38550 | chr2:178583664;178583663;178583662 | chr2:179448391;179448390;179448389 |
| Novex-1 | 12900 | 38923;38924;38925 | chr2:178583664;178583663;178583662 | chr2:179448391;179448390;179448389 |
| Novex-2 | 12967 | 39124;39125;39126 | chr2:178583664;178583663;178583662 | chr2:179448391;179448390;179448389 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/E | None | None | 0.879 | N | 0.699 | 0.371 | 0.748702547252 | gnomAD-4.0.0 | 1.59513E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.7922E-05 | None | 0 | 0 | 0 | 0 | 0 |
| V/I | rs770780646  |
0.024 | 0.001 | N | 0.207 | 0.069 | 0.288352970974 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.88E-05 | None | 0 | 0 | 0 |
| V/I | rs770780646 |
0.024 | 0.001 | N | 0.207 | 0.069 | 0.288352970974 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07469E-04 | 0 |
| V/I | rs770780646 |
0.024 | 0.001 | N | 0.207 | 0.069 | 0.288352970974 | gnomAD-4.0.0 | 3.72184E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.48097E-07 | 4.40267E-05 | 1.60344E-05 |
| V/L | rs770780646 |
None | 0.031 | N | 0.401 | 0.095 | 0.26547132957 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/L | rs770780646 |
None | 0.031 | N | 0.401 | 0.095 | 0.26547132957 | gnomAD-4.0.0 | 6.57601E-06 | None | None | None | None | I | None | 2.41243E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.4016 | ambiguous | 0.3334 | benign | -0.311 | Destabilizing | 0.296 | N | 0.459 | neutral | N | 0.412698131 | None | None | I |
| V/C | 0.8398 | likely_pathogenic | 0.7818 | pathogenic | -0.749 | Destabilizing | 0.991 | D | 0.573 | neutral | None | None | None | None | I |
| V/D | 0.7726 | likely_pathogenic | 0.6834 | pathogenic | -0.262 | Destabilizing | 0.906 | D | 0.725 | prob.delet. | None | None | None | None | I |
| V/E | 0.7039 | likely_pathogenic | 0.6417 | pathogenic | -0.387 | Destabilizing | 0.879 | D | 0.699 | prob.neutral | N | 0.468379817 | None | None | I |
| V/F | 0.3232 | likely_benign | 0.2392 | benign | -0.703 | Destabilizing | 0.826 | D | 0.564 | neutral | None | None | None | None | I |
| V/G | 0.4159 | ambiguous | 0.3408 | ambiguous | -0.367 | Destabilizing | 0.879 | D | 0.709 | prob.delet. | N | 0.512803623 | None | None | I |
| V/H | 0.8589 | likely_pathogenic | 0.7872 | pathogenic | 0.016 | Stabilizing | 0.991 | D | 0.741 | deleterious | None | None | None | None | I |
| V/I | 0.0823 | likely_benign | 0.0741 | benign | -0.315 | Destabilizing | 0.001 | N | 0.207 | neutral | N | 0.45089116 | None | None | I |
| V/K | 0.748 | likely_pathogenic | 0.6867 | pathogenic | -0.306 | Destabilizing | 0.906 | D | 0.703 | prob.neutral | None | None | None | None | I |
| V/L | 0.31 | likely_benign | 0.2424 | benign | -0.315 | Destabilizing | 0.031 | N | 0.401 | neutral | N | 0.517942871 | None | None | I |
| V/M | 0.266 | likely_benign | 0.2009 | benign | -0.483 | Destabilizing | 0.826 | D | 0.529 | neutral | None | None | None | None | I |
| V/N | 0.547 | ambiguous | 0.4658 | ambiguous | -0.117 | Destabilizing | 0.967 | D | 0.725 | prob.delet. | None | None | None | None | I |
| V/P | 0.8645 | likely_pathogenic | 0.8196 | pathogenic | -0.285 | Destabilizing | 0.967 | D | 0.699 | prob.neutral | None | None | None | None | I |
| V/Q | 0.668 | likely_pathogenic | 0.5965 | pathogenic | -0.346 | Destabilizing | 0.967 | D | 0.707 | prob.neutral | None | None | None | None | I |
| V/R | 0.6466 | likely_pathogenic | 0.5884 | pathogenic | 0.148 | Stabilizing | 0.906 | D | 0.723 | prob.delet. | None | None | None | None | I |
| V/S | 0.4725 | ambiguous | 0.4021 | ambiguous | -0.43 | Destabilizing | 0.906 | D | 0.63 | neutral | None | None | None | None | I |
| V/T | 0.4375 | ambiguous | 0.3742 | ambiguous | -0.463 | Destabilizing | 0.575 | D | 0.518 | neutral | None | None | None | None | I |
| V/W | 0.9249 | likely_pathogenic | 0.8769 | pathogenic | -0.755 | Destabilizing | 0.991 | D | 0.757 | deleterious | None | None | None | None | I |
| V/Y | 0.7715 | likely_pathogenic | 0.6805 | pathogenic | -0.471 | Destabilizing | 0.906 | D | 0.554 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.